Infection with the AIDS retrovirus (ARV) has been associated with development of peripheral nerve disease. Although neuropathy may affect 5-10% of AIDS patients, the clinical and pathologic findings are incompletely characterized. In many patients with AIDS a painful sensory neuropathy is a late manifestation of the illness. By contrast, we have recently identified a sizeable subgroup of ARVseropositive patients in whom a demyelinating motor neuropathy is the presenting manifestation; most of these patients lack adenopathy, weight loss or other AIDSrelated complex symptoms. The disorder is often selflimited and responsive to treatment by plasmapheresis. These patients closely resemble patients with acute inflammatory demyelinating polyneuropathy and chronic inflammatory polyneuropathy who are ARVseronegative. Finally, a third subgroup of patients appears to have multiple mononeuropathy due to vasculitis. The proposed studies will test the hypothesis that in ARVseropositive patients these three categories of peripheral nerve disease can be distinguished. The studies will examine pathogenetic mechanisms for each subgroup. We postulate that the demyelinating motor neuropathy subgroup has an immunopathogenetic basis, that the late sensory neuropathy may be due to ARV infection of dorsal root ganglia, and that the multiple mononeuropathy may have an angiopathic basis, probably due to vasculitis. Clear separation of these clinical syndromes should provide improvements in diagnosis and management of peripheral nerve disease in ARV infection. Delineation of the pathogenic mechanisms in these patients may provide insights into mechanisms of peripheral neuropathies in general.